Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions

Abstract Bacterial vaginosis (BV) is the most prevalent vaginal condition among reproductive-age women presenting with vaginal complaints. Despite its significant impact on women’s health, limited knowledge exists regarding the microbial community composition and metabolic interactions associated wi...

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Main Authors: Lillian R. Dillard, Emma M. Glass, Glynis L. Kolling, Krystal Thomas-White, Fiorella Wever, Robert Markowitz, David Lyttle, Jason A. Papin
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59965-y
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author Lillian R. Dillard
Emma M. Glass
Glynis L. Kolling
Krystal Thomas-White
Fiorella Wever
Robert Markowitz
David Lyttle
Jason A. Papin
author_facet Lillian R. Dillard
Emma M. Glass
Glynis L. Kolling
Krystal Thomas-White
Fiorella Wever
Robert Markowitz
David Lyttle
Jason A. Papin
author_sort Lillian R. Dillard
collection DOAJ
description Abstract Bacterial vaginosis (BV) is the most prevalent vaginal condition among reproductive-age women presenting with vaginal complaints. Despite its significant impact on women’s health, limited knowledge exists regarding the microbial community composition and metabolic interactions associated with BV. In this study, we analyze metagenomic data obtained from human vaginal swabs to generate in silico predictions of BV-associated bacterial metabolic interactions via genome-scale metabolic network reconstructions (GENREs). While most efforts to characterize symptomatic BV (and thus guide therapeutic intervention by identifying responders and non-responders to treatment) are based on genomic profiling, our in silico simulations reveal functional metabolic relatedness between species as quite distinct from genetic relatedness. We grow several of the most common co-occurring bacteria (Prevotella amnii, Prevotella buccalis, Hoylesella timonensis, Lactobacillus iners, Fannyhessea vaginae, and Aerrococcus christenssii) on the spent media of Gardnerella species and perform metabolomics to identify potential mechanisms of metabolic interaction. Through these analyses, we identify BV-associated bacteria that produce caffeate, a compound implicated in estrogen receptor binding, when grown in the spent media of other BV-associated bacteria. These findings underscore the complex and diverse nature of BV-associated bacterial community structures and several of these mechanisms are of potential significance in understanding host-microbiome relationships.
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spelling doaj-art-d1b4be75469f47c69a8ebb25ecebf7f02025-08-20T03:48:18ZengNature PortfolioNature Communications2041-17232025-05-0116111110.1038/s41467-025-59965-yGenome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactionsLillian R. Dillard0Emma M. Glass1Glynis L. Kolling2Krystal Thomas-White3Fiorella Wever4Robert Markowitz5David Lyttle6Jason A. Papin7Department of Biochemistry & Molecular Genetics, University of VirginiaDepartment of Biomedical Engineering, University of VirginiaDepartment of Biomedical Engineering, University of VirginiaEvvyEvvyEvvyEvvyDepartment of Biochemistry & Molecular Genetics, University of VirginiaAbstract Bacterial vaginosis (BV) is the most prevalent vaginal condition among reproductive-age women presenting with vaginal complaints. Despite its significant impact on women’s health, limited knowledge exists regarding the microbial community composition and metabolic interactions associated with BV. In this study, we analyze metagenomic data obtained from human vaginal swabs to generate in silico predictions of BV-associated bacterial metabolic interactions via genome-scale metabolic network reconstructions (GENREs). While most efforts to characterize symptomatic BV (and thus guide therapeutic intervention by identifying responders and non-responders to treatment) are based on genomic profiling, our in silico simulations reveal functional metabolic relatedness between species as quite distinct from genetic relatedness. We grow several of the most common co-occurring bacteria (Prevotella amnii, Prevotella buccalis, Hoylesella timonensis, Lactobacillus iners, Fannyhessea vaginae, and Aerrococcus christenssii) on the spent media of Gardnerella species and perform metabolomics to identify potential mechanisms of metabolic interaction. Through these analyses, we identify BV-associated bacteria that produce caffeate, a compound implicated in estrogen receptor binding, when grown in the spent media of other BV-associated bacteria. These findings underscore the complex and diverse nature of BV-associated bacterial community structures and several of these mechanisms are of potential significance in understanding host-microbiome relationships.https://doi.org/10.1038/s41467-025-59965-y
spellingShingle Lillian R. Dillard
Emma M. Glass
Glynis L. Kolling
Krystal Thomas-White
Fiorella Wever
Robert Markowitz
David Lyttle
Jason A. Papin
Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions
Nature Communications
title Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions
title_full Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions
title_fullStr Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions
title_full_unstemmed Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions
title_short Genome-scale metabolic network reconstruction analysis identifies bacterial vaginosis-associated metabolic interactions
title_sort genome scale metabolic network reconstruction analysis identifies bacterial vaginosis associated metabolic interactions
url https://doi.org/10.1038/s41467-025-59965-y
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